Chronic Kidney Disease Influences Multiple Systems: Describing the Relationship between Oxidative Stress, Inflammation, Kidney Damage, and Concomitant Disease

Figure 3

Interactions between radical damage, inflammation, and distal injury. Intermediates in grey initiate damage of the molecular components of renal tissue. Compounds in white, although not directly damaging, are involved in harmful reactions. Damage resulting from intermediates in grey promotes an inflammatory response during which additional superoxide is released via phagocytic NADPH oxidase activity. If sustained, this process may lead to a systemic inflammatory response that can result in damage to tissues that are distal to the kidney, such as the pancreas (type 2 diabetes) and vasculature (cardiovascular disease), via related increases in the production of reactive oxygen species (ROS). For example, the transcription of NF-B-dependent genes may regulate levels of cellular ROS; the NF-B pathway may be activated by stimulation of proinflammatory receptors, such as the TNF receptor superfamily. In turn, NF-B activation may also be regulated by cellular levels of ROS; ROS can activate NF-B through alternative IB phosphorylation, resulting in the degradation of IB.